[Allopurinol in the prevention and treatment of urate complications in leukemia].
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Biomedical subjects
Publications and source records attributed to M Roberto.
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Specific receptors for pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide with neuroregulatory and neurotrophic functions, have been identified recently in different brain regions, including the hippocampus. In this study, we examined the effects of PACAP-38 on the excitatory postsynaptic field potentials (fEPSPs) evoked at the Schaffer collateral-CA1 synapses. Brief bath application of PACAP-38 (0.05 nM) induced a long-lasting facilitation of the basal transmission. Enhancement of this response was occluded in part by previous high-frequency-induced long-term potentiation (LTP). PACAP-38 did not significantly alter the paired-pulse facilitation (PPF). PACAP-38 has been shown to have a presynaptic effect on the septohippocampal cholinergic terminals, which results in an increase in basal acetylcholine (ACh) release. To assess whether the PACAP-38 enhancement of CA1 synapses was related to the activation of the cholinergic system we examined the effect of this peptide in the presence of atropine, a muscarinic receptor antagonist. The enhancement of the fEPSPs by PACAP-38 was blocked by bath application of atropine. These results show that PACAP-38 induces facilitation of hippocampal synaptic transmission through activation of the cholinergic system via the muscarinic receptors.
Pituitary adenylate cyclase-activating polypeptide (PACAP-38) is a member of the vasointestinal polypeptide (VIP)/secretin/glucagon family of neuropeptides for which neuroregulatory functions have been postulated. PACAP-38 receptors are expressed in different brain regions, including hippocampus. In this study, we examined the dose-dependent effects of PACAP-38 on the excitatory postsynaptic field potential (fEPSP) evoked at the Schaffer collateral-CA1 synapse in rat hippocampal slices. Bath application of low dose (0.05 nM) of PACAP-38 induced long-lasting facilitation of the fEPSP. This enhancement was blocked by the cholinergic receptor antagonist atropine and partially by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) and therefore, shares a common mechanism with LTP. In contrast, a high dose (1 microM) of PACAP-38 induced a persistent depression of the fEPSP that was not blocked by antagonists of cholinergic receptors (i.e., atropine and mecamylamine), adenosine receptors (i.e., DCPCX), or glutamatergic NMDA receptors (APV). Intermediate doses (0.1-0.5 microM) of PACAP-38 produced an initial decrease of the fEPSP followed by an enhancement. This decrease was not blocked by atropine whereas the facilitation was. These results show that PACAP-38 modulates CA1 synaptic transmission in a dose-dependent manner and that the peptide interacts with cholinergic and glutamatergic systems.
The postnatal bone growth (appositional and internal) in the auditory ossicles and in the tibia of three mongrel dogs was studied by means of tetracycline and alizarin labeling. The appositional growth is characterized by an increase in the external dimensions of the auditory ossicles within the first month of postnatal life. No trace of bone deposition was found after this period of time. The patterns of internal growth are: 1) the rate of primary osteon formation shows the same value in the incus and malleus; 2) these values are always less than those in the primary osteons of the diaphysis of the tibia of the same dog; 3) the time required for the formation of these osteons in the auditory ossicles, like in the other parts of the skeleton, increases significantly with age.
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The amount and distribution of the post-natal bone deposition in the auditory ossicles and in the left tibia of dogs of varying ages were studied by means of alizarin labelling. The relative amount of fluorescent new-formed bone was expressed as a percentage ratio NB/(NB+PB) of new bone (NB) on the pre-existing bone (PB). The result was that the post-natal bone deposition (1) was larger in the tibia than in the incus, malleus and stapes; (2) significantly decreased with age both in the ossicles and in the tibia; (3) in the stapes it stopped at 3 months, while it was present in the tibia, incus and malleus even at 12 months. In the ossicles the post-natal bone deposition takes place both on the periosteal surfaces of the ossicles and on the internal surfaces of the haversian systems. The first process produces an appositional growth that stops in all three ossicles within the 1st month of post-natal life, the second one produces an internal growth that continues until the age of three months in the stapes, while in the incus and malleus it occurs in small amounts, even in the 12th month of life. In the ossicles all the new-formed bone tissue, periosteal and osteonic, is built up by primary bone (addition bone). In the tibia from 50 days of age the primary bone is gradually replaced by secondary haversian systems as a consequence of remodelling processes.
Admittance component curves were studied in a series of 14 fresh human temporal bones with perfectly normal tympanic membrane, before and after experimental lesions. The lesions were all performed in successive steps in each temporal bone and consisted in section of ligaments and tendons, interruptions and fixations of the ossicular chain. The results obtained demonstrate that the tympanograms traced in fresh human temporal bones, before and after experimental lesions, are quite similar to those observed respectively in normal and pathological living ears. (a) The 'pre-experimental' tympanograms showed A-type curves with peak and admittance component values well within the range of normal living ears; (b) the tympanogram peak values increased very little and remained in the range of normal ears also after section of ligaments and tendons; (c) the ossicular chain interruptions always resulted in A-type curves at 220 Hz and in W-pattern ones at 660 Hz wherever the interruptions occurred; (d) the ossicular chain fixations always exhibited A-type tympanograms with decreased peak and admittance component values; (e) finally, the condition of the Eustachian tube, closed or opened, did not change the shape of the tympanograms; the notch depth of the curves traced with opened tube, became higher than those obtained with closed tube.
Interaction between continuous and impulse noise was studied. One group of chinchillas was exposed to octave band of noise of 0.5 kHz 95 dB SPL intensity. Three groups were exposed to impulse noises of 113, 119 and 125 prak SPL emitted at 1 imp/sec, 1 imp/4 sec and 1 imp/16 sec respectively. Three groups were exposed to noise created by a combination of above continuous and impulse noises. All exposures lasted for 5 days. Hearing thresholds were measured in 35 animals using auditory evoked potentials. The combined continuous and impulse noises showed equal energy contents, but the groups exposed to 119 and 125 dB impulse noise intensities developed an exacerbation of PTS and cell hair loss. Therefore, the critical level, under which the damage associated with noise exposure is related to the total noise energy (Equal Energy Hypothesis) was reduced when impulse noise was added to continuous noise.
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In industrial setting impulse noise rarely occurs in isolation. Impulses are more often superimposed on a background of continuous noise. Since measurement of peak sound pressure level or energy considerations may not provide a sufficient index of danger to hearing, examining the frequency spectra of the noises appeared to be important. Seven groups of five chinchillas were used in this study. Four groups were exposed to octave bands of noise centered at 0.5, 2 or 4 kHz having intensities of 95, 90 and 86 dB SPL respectively or impulse noise of 113 dB peak SPL applied on time per 1 second. Three groups were exposed to the combination of impulse noise and one of the above continuous noises. Each exposure lasted five days. PTS was calculated on each animal using auditory evoked potentials. The cochleas were dissected and evaluated using conventional histological surface preparation and examined with scanning electron microscopy (SEM) employing a JEOL 35 microscope. The groups exposed to only the impulse or to continuous noise alone developed neither PTS nor hair cell loss. Considerable values of PTS and sensory cell loss were observed in animals exposed to impulse noise in combination with 2 and 4 kHz of continuous noise. This interaction effect increases as the spectral overlapping between the impulse and continuous noise increases. In these animals excellent information concerning the sensory cell losses or cell damage was obtained with SEM. The results of the present study demonstrate that interaction between impulse and continuous noise can indicate increased hazard, which is highly dependent not only upon the total energy of the complex exposure but also on the degree of spectral overlapping between impulse and continuous noise.
Dogs from the same litter, divided into three groups aged 10, 25, and 50 days, received an intraperitoneal injection of tetracycline for two successive days. The temporal bones were fixed, embedded in methylmethacrylate, sectioned in to a single 100 microns thick section along the main axis of the anterior and lateral semicircular canals, grounded by hand to 30 microns and observed at UV light. The new bone tissue is laid down both at the endosteal and endochondral bone of the anterior and lateral semicircular canals. The bone deposition decreases with the age of the animal and earlier at the endosteum than at the endochondral bone.